ANTINEMATODALS

Copyright, Purdue Research Foundation, 1996

| BMS 445 Intro | | Drug Groups | | Slides / Graphics | | Address | | E-mail | | Antiparasitics Intro. | | Antinematodals Toxicity |

Overview

Drug Groups and General Mechanisms

Chemical Groups, Members, and General Indications
Group
Drugs
General Indications1
Macrolide Endectocides
  • Ivermectin, Animal: EqvalanR, Heartgard 30R, and IvomecR; Human: MectizanR
  • Milbemycin Oxime, InterceptorR
  • Moxidectin, CydectinR
  • Doramectin
  • Abramectin
  • Extremely broad -- nematodes & arthropods
  • Filarids, e.g., Dirofilaria immitis larvae
  • Gastrointestinal parasites
  • Lungworms
  • Skin, e.g., Onchocerca,, grubs, lice, mites
Benzimidazoles
  • Thiabendazole
  • Albendazole
  • Fenbendazole
  • Mebendazole
  • Oxibendazole
  • Broad spectrum of nematodes
  • Albendazole -- trematodes (e.g., flukes like Fasciola hepatica), protozoans (e.g., Giardia spp.)
  • Mebendazole -- nematodes, cestodes, protozoans
Probenzimidazoles
  • Febantel, RintalR
    yields febendazole and oxfendazole
  • Netobimin
  • Approved horses, dogs, cats
  • Broad spectrum
  • nematodes ruminants, swine, some zoo animals
  • Combined with other drugs for dogs and cats
    • Feb. + praziquantel -- Vercom PasteR
    • Feb. + praziquantel & pyrantel pamoate -- Drontal Plus R
Imidazothiazoles
  • Levamisole
  • Broad spectrum
  • Nematodes, GI and lungs
  • D. immitis microfilariae
Pyrimidines
  • Pyrantel pamoate, CombantrinR
  • Pyrantel tartrate, BanminthR, NemexR, Strongid-TR, StrongidR
  • Morantel tartrate, RumantelR, NemantelR, StrongidR
  • Pyrantel: dogs, horses, and swine, for ascarids, hookworms, and strongyles
  • Morantel: cattle for Haemonchus, Ostertagia, Trichostrongylus, Cooperia, Nematodirus, and Oesophagostomum.
  • Tartrates: rapidly absorbed
  • Pamoate: poorly / slowly absorbed
Substituted Piperazines
  • Piperazine
  • Diethylcarbamazine citrate, (DEC) CaracideR, HetrazanR, etc.
  • DEC: D. immitis larvae
  • PIP: Ascarids very sensitive
Organophosphate
  • Dichlorvos, TaskR, Atgard-VR
  • Trichlorfon
  • Coumaphos
  • Crufomate
  • Haloxon
  • Bots
  • Ascarids
  • Cestodes
  • Insects and arachnids.
Trivalent Arsenicals
  • Thiacetarsamide sodium(Caparsolate sodium), (Caparsolate sodium), FilaramideR, ArsenamideR
  • Melarsomine, ImmiticideR
  • Adult D. immitis
1Note: Indications may not apply to all members of the group equally. There may be dose forms for some indications and species, but not others. Note also that details of larvae vs adults are not noted in every case.
Refs: Barragry'95
Webster, LT, Jr., GG8th'90
USPDI'94
Courtney & Roberson'95





























Chemical Groups and General Mechanisms of Antinematodal Drugs
Group/Drug
Mechanism
Effect on Parasite
Macrolide Endectocides
  • CURRENT1:
  • Open chloride channels in invertebrates
  • Binding site GLUTAMATE-gated channels
  • Site is near GABA-gated sites which may also be potentiated
  • 50% of effect reversed with picrotoxin, a GABA antagonist active at the chloride channel
  • Nematodes: interneurons and excitatory motor neurons
  • Arthropods: myoneural junction
  • Mammals: GABA-mediated transmission in CNS
  • ALL: Chloride current causes hypERpolarization

  • FORMER:
  • Increase release of GABA from neurons
  • GABA potentiation
Flaccid paralysis
Benzimidazoles
  • Not clearly delineated
  • Relative importance of each may depend on derivative
  • Degeneration of microtubules
  • Inhibit glucose transport and uptake
  • Interfere with energy production
  • Inhibit fumarate reductase
  • Starvation of parasite -- energy processes
  • Ovicidal
  • Cytoplasmic microtubules disappear in tegumentary and intestinal cells.
  • Secretory processes, e.g., from Golgi apparatus and acetylcholine release, are impaired.
  • Microtubular function may be common to all of these processes.
Probenzimidazoles
  • See benzimidazoles
  • See benzimidazoles
Imidazothiazoles
  • Typical concentrations:
    Nicotinic sitmulation of ganglia and CNS
  • Higher concentrations:
    interferes with fumarate reductase and succinate oxidase of nematodes
  • Immunostimulant -- only indication in humans
  • Spastic paralysis
  • Parasites may be expelled alive
Pyrimidines, e.g., pyrantel
  • Nicotinic action at NM Junction
  • Depolarizing neuromuscular blocking agents.
    Contrast to piperazine -- antagonistic?(!)
  • Inhibits cholinesterases
  • Slowly developing spastic paralysis
Substituted Piperazines
  • Hyperpolarization of muscle membrane
  • Flaccid paralysis
Organophosphates
  • Irreversible Acetylcholinesterase inactivation, thus buildup of ACh at sites where it is being released
  • Also inhibits other cholinesterases
  • Spastic paralysis
Trivalent Arsenicals
  • Sulfhydryl reagents
  • React with molecules having -SH to form covalent bonds
  • Pyruvate dehydrogenase system especially sensitive
  • Deprive parasite of energy
  • Other ramifications of reacting with -SH groups
  • Kill adults
1Courtney & Roberson'95
Barragry'95
Webster, LT, Jr., GG8th'90
USPDI'95

Macrolide Endectocides

The first member of the anthelmintic macrolides to be commercially available was ivermectin. Dose forms are now available for many species. Some sample trade names are: Eqvalan, Heartgard 30, and Ivomec. Moxidectin is a macrolide that is available in other countries and may soon be sold in the U.S. (Lynn'95).

IVERMECTIN

Structure

Spectrum

Ivermectin has one of the broadest clinical antiparasitic spectrums known. It includes gastrointestinal parasites such as ascarids, adult large strongyles, adult/4th stage larvae of small strongyles, pinworms, large stomach worms, hair worms, and immature stages of stomach bots. It is also effective against parasites that end up in the skin or lungs. For example, the immature form of onchocerca, which causes summer dermatitis in horses, is removed as are lung worms. Several parasites that live in or on the skin are also affected, e.g., cattle grubs, lice, and mites. Some stages of some blood borne filarids, e.g., immature Dirofilaria immitis, are removed.

Mechanism of Action

Ivermectin causes tonic paralysis of peripheral musculature in nematodes and ectoparasites (ticks, mites, insects). It potentiates release and action of GABA. In vertebrates such neurons and receptors are in the CNS where ivermectin achieves low concentrations. Ivermectins are ineffective in cestodes and trematodes, perhaps because they lack GABA-mediated control of peripheral musculature.

Although well absorbed from the gastrointestinal tract, they cross the blood brain barrier poorly. They are eliminated primarily in the feces in animals. There is little data from human studies.

Adverse effects

Ivermectins are relatively safe for species that have an approved dose form; horse, dog, cattle, and swine. They have no known teratogenic effect in these species. There is evidence of substantial teratogenicity in mice, rats, and rabbits, the species most commonly used for preclinical testing. (Brown '96)

At high doses the ivermectins can cause CNS signs, including lethargy, ataxia, mydriasis, tremors, and death.

Adverse effects, in horses, of an injectable form that is no longer avilable may represent signs that could be seen with overdose (Louisiana study). These signs include eyelid edema, fever, increased rate and depth of respiration, disorientation, signs of colic, extreme depression, and death within minutes. Death occurred in 1 horse of 3,316 treated.

DOGS, ESPECIALLY COLLIES(Boraski, 1984) were claimed to have special sensitivity to ivermectin. Some collie strains developed severe adverse reactions when given ivermectin at a dose of 100 mcg/kg; 16 x the label dose now recommended. At a dose of 6 mcg/kg (the approved dose), the drug is well tolerated in collies and other breeds of dogs (Lynn'95, p266). A single PO dose of 2 mg/kg and PO doses of 0.5 mg/kg q1d for 14 weeks were well tolerated by dogs. Doses greater than 20 mg/kg given to laboratory dogs causes mydriasis, depression, tremors, ataxia, coma, and death. No teratogenic effects where observed after giving pregnant bitches repeated PO doses of 0.5 mg/kg. (Note: Some doses in this paragraph were previously in error because they were listed as "mg" instead of "mcg". The author apologizes for this oversight.)

There is now a special tablet formulation, HEARTGARD 30 (Merck) for use in preventing heartworms so there is no longer any reason to use dose forms prepared for other species. Nonetheless, because it underscores a major principle of therapy, the following anecdote is worth reading.

<<< AN IVERMECTIN STORY >>>
The following is an excerpt from a letter written by a practitioner. (Schulze 1984) "...Recently at the suggestion of a sales representative, I gave an injection of Eqvalan to a heavily parasitized canine pup of a large mixed breed (not Collie). Approximately 0.15 cc was given deep intramuscularly (gastrocnemius). The animal appeared in otherwise good health at presentation. Within one hour, an agitated client returned with a critically ill animal. It exhibited just about every imaginable sign, from prostration, ptyalism, opisthotonos, nystagmus, thrashing and paddling, extensor rigidity, to coma and death within another 15 minutes. It was like watching every page of a veterinary toxicology text flashing before my eyes. Forget the LD-50s!

"This embarrassed veterinarian has given his first and last ivermectin injection to a canine. Needless to say, I am hesitant to continue my 0.2% ivermectin oral regimen of successful heartworm control in the same species." [end of quote]

<<< MORALS >>>
Certain morals can be drawn from this anecdote. First, be extremely cautious when using new drugs in species other than those for which they were specifically approved. Second, route of administration and dose formulation do make a difference and are often species specific. <<< MORALS >>>

Many studies have shown that although ivermectin is not approved for use in cats, single PO doses of 0.024 mg/kg are effective against Ancylostoma braziliense and Ancylostoma tubaeforme. A dose of 0.3 mg/kg is required for Toxocara cati. Doses of 0.024 mg/kg were shown to be effective in preventing Dirofilaria immitis adults from appearing in infected cats when given 30 to 45 days after artificial infection. Thus, this drug and dose should be satisfactory as a heartworm preventive when given q1mo (Lynn'95).

Advantages

Advantages of ivermectin include its broad spectrum of action, its effectiveness against many immature forms, and its lack of cross-resistance with other major anthelmintic groups, e.g., the benzimidazoles and cholinesterase inhibitors.

Many dose forms are now available including an injectable for swine and cattle; an oral paste for horses; and an oral tablet for dogs. The tablet for dogs is intended for heartworm prevention and is given only once per month. Collies have a reputation for being especially sensitive to the effects of ivermectin, but the oral dose form can be used in them at recommended doses.

Disadvantages

Disadvantages appear to be few, but the drug is very expensive. Moreover, it is still sufficiently new that its true warts may not have been appreciated.

Milbemycin oxime (InterceptorR)

Ref: Lynn'95, p267.

Moxidectin (CydectinR)

Moxidectin is a new macrolide that is being used in South America. Its commercial introduction into the U.S. is pending (Lynn'95). It is effective against a wide variety of parasites.

IM to horses: Gasterophilus intestinalis, Parascaris equorum, Strongylus vulgaris, Strongylus edentatus, Oxyuris equi, Habronema muscae.

PO to cattle: 99% effect on adult and 4th stage Ostertagia ostertagi, Cooperia spp., Nematodirus helvetianus. Adult Trichostrongylus ... LONG LIST).

PO to sheep

PO to Dogs: D. immitis and hookworms (Ancylostoma caninum and Uncinaria stenocephala), Toxacara canis, and Toxascaris leonina.

Benzimidazoles

Eight benzimidazoles are available for clinical use including: thiabendazole, mebendazole, fenbendazole, cambendazole, oxibendazole, flubendazole, oxfendazole, and albendazole. In addition, there are pro-benzimidazoles. These are prodrugs that yield benzimidazoles after biotransformation. Febantel is an example. It yields febendazole and oxfendazole following injection (Armour 1983). (See structures below)

Less soluble derivatives, e.g., albendazole, fenbendzole, and oxfendazole, appear to be more effective because of the increased exposure afforded by the prolonged dissolution in the gut. For the others especially, repeated administration with small dose intervals seems to increase their effectivess because of the increased exposure (Armour 1983). Armour states that because the rumen acts as a slow release site for these drugs to the lower gi tract, they are more effective in ruminants than other species. Representatives, such as mebendazole, have poor bioavailability so systemic actions are minimal. In fact, these may be part of the reason for their low toxicity. Others, such as thiabendazole, are rapidly absorbed and are eliminated in the urine.

Spectrum

The benzimidazoles have such a broad spectrum of action that it is useless to list it. Some tapeworms and bots are resistant. There is also variation among the members as to which is more effective, e.g., against tapeworms or flukes than the others. Mebendazole has good activity against many tapeworms. Albendazole has activity against flukes like Fasciola hepatica.


Mechanism of Action

The mechanism of action of benzimidazoles is not clearly delineated and may differ from one member of the group to another. Interference with microtubular function and inhibition of helminth-specific mitochondrial fumarate reductase system have both been described. Thiabendazole may have both actions. Mebendazole may only bind to tubulin.

Inhibition of the fumarate reductase would interfere with energy production in the parasite. Binding to tubulin may impair many processes. Cytoplasmic microtubules disappear in tegumentary and intestinal cells. Secretory processes, e.g., from Golgi apparatus and acetylcholine release, are impaired. Glucose uptake by cells is decreased. Microtubular function may be common to all of these processes. These processes are not significantly altered in host cells although the mechanism of selectivity may be differential binding to subunits of tubulin, this is not proven for all benzimidazoles.

Adverse effects

Teratogenic effects have been shown for albendazole, cambendazole, oxfendazole, and parbendazole. If these drugs are to be used in early pregnancy, it must be for good reason and at the lowest recommended doses.

Acute toxicity is extremely difficult to produce with these drugs and LD50s are almost impossible to define for drugs such as thiabendazole and fenbendazole. They are regarded as safe up to 20 to 30 times the recommended dose. The earliest sign of toxicity noted in horses with mebendazole is a slight diarrhea.

Cambendazole produces idiosyncratic reactions that have caused it to be removed from the market in some countries. (USA)

Advantages

Advantages of benzimidazoles include their palatability, safety, and broad spectrum.

Disadvantages

Disadvantages include the increasing resistance of parasites to this group of drugs. Furthermore, there is significant cross-resistance among the members.

Febantel

Febantel [Rintal ]is a pro-benzimidazole which yields both fenbendazole and oxfendazole. Its spectrum includes Strongyles, oxyurids, and ascarids of horses. There are no known contraindications, but several species of cyathostomes are reported to be resistant. The dose must be increased to 50 mg/kg from the normally used 6 mg/kg eliminate Strongyloides westeri from foals. The drug has a wide margin of safety in both young and old horses, stallions, and pregnant mares. It can be given with trichlorfon to control bots. It is available as a paste and as a suspension.

Pyrimidine derivatives

Pyrantel and Morantel are the members of this group. The basis of difference between them and the various dose forms in which they are available is solubility in the gut. Oxantel belongs to the same group and is used in humans for trichuriasis.

Pyrantel is available as the pamoate and tartrate derivative. Combantrin is pyrantel pamoate. Banminth, Nemex, Strongid-T, and Strongid-P are examples of pyrantel tartrate. Pyrantel tartrate is rapidly absorbed from the gut. Pyrantel pamoate is poorly absorbed. The pyrantel salts are stable in solid form, but not in solution. Because they are photodegradable they must be used quickly once opened.


Morantel is available as the tartrate. Rumantel, Nemantel, and Strongid are examples of morantel tartrate.

Mechanism of Action

Parasites exhibit spastic paralysis and apparently cannot maintain their position. Paralysis is caused by nicotinic action at neuromuscular junction of parasites, i.e., these drugs are depolarizing neuromuscular blocking agents. The depolarization leads to increased contraction of parasite muscles. Note that piperazine causes hypERpolarization which would lead to decreased spike frequency and contraction. Thus, piperazine and pyrantel would be expected to be antagonistic. Pyrantel can also cause complete neuromuscular blockade in animals if dose is high enough. At recommended doses, this is not a hazard.

Spectrum

Morantel is used in cattle for Haemonchus, Ostertagia, Trichostrongylus, Cooperia, Nematodirus, and Oesophagostomum.

Pyrantel is used in dogs, horses, and swine, for ascarids, hookworms, and strongyles.

Adverse effects

No adverse effects were described by Theodorides, 1985. However, at increasing doses, one would expect signs of neuromuscular blockade or other evidence of nicotinic action. For example, in humans, oral doses may cause transient, mild gastrointestinal signs.

Contraindications

of morantel include dairy cows, for which it is not approved [Need to check '95] . Pyrantel should not be mixed with rations containing bentonite. (Bentonite is a soft, porous clay from volcanic ash.)

Precautions/comments

Withdrawal times are: morantel in cattle, 14 days; pyrantel in pigs, 24 hours.

Should not use pyrantel, morantel and levamisole together. Pyrantel is mutually antagonistic with piperazine on membrane potential, but can be used with organophosphates and certain other antiparasitic and antimicrobial drugs. Pyrantel can be used in the presence of Dirofilaria immitis. It can also be used in pregnancy, nursing, weanlings, and males used for breeding.

Advantages

Morantel is effective against adult gastrointestinal parasites of cattle.

Pyrantel is non-toxic and has a short withdrawal time in swine. It is the only APPROVED anthelmintic that, when fed continuously, kills just-hatched larvae of A. suum in gut to prevent appearance of milk spots on liver of pigs.

Disadvantages

Morantel is not too good against larval forms in cattle. Pyrantel should not be used in severely debilitated animals. May cause vomiting in smal animals.

Organophosphates

Major examples of organophosphates include dichlorvos, trichlorfon, and coumaphos.

Mechanism of Action


Value of resins

Irreversible inactivation of acetylcholinesterase, leading to excessive cholinergic activity at relevant sites. It would be expected to reduce plasma cholinesterase activity to minimal levels, thus making the host more susceptible to other cholinomimetic agents and cholinesterase inhibitors.

Spectrum

Organophosphates are effective against bots, ascarids, and tapeworms. They are also used topically against insects and arachnids.

Adverse effects

The adverse effects are discussed with special reference to dichlorvos. Those of other organophosphates will be very similar.

The margin of safety is very narrow. The drugs are safe to approximately 2-times the recommended dose.

Signs of toxicity are typical of acetylcholinesterase inhibitors and include evidence of excessive acetylcholine at muscarinic and nicotinic receptors. Early signs include salivation, lacrimation, urination, dyspnea, and defecation which have the mnemonic of SLUDD. Treatment is with atropine and pralidoxime.

Formulations of the organophosphate compounds are very specific for the target species, especially in flea collars and in the resins intended for oral administration. For more information on why a resin formulation intended for one species might be toxic or ineffective when given to another species consult Roberson (JBM5th 830-831).

A summary of the Roberson material follows. Dichlorvos is formulated in resins to make a slow release dose form. Variations in geometry, size and method of formulation (including coating or not coating), of pellet plus the quantity of dichlorvos allow for a range of diffusion rates suitable for different host animals. Task, for the dog, has smaller pellets and faster release rate to accomodate the shorter gastrointestinal tract. For swine, Atgard V has larger pellets and a moderate release rate for the longer tract. Pellets may contain 20% dichlorvos. A moderate release rate may cause 50-55% loss during passage through the tract of swine in 24 hours. Usually, enough dichlorvos is eliminated in the feces to be effective as an insecticide for fly larvae.

Two principle difficulties associated with dichlorvos are overcome by resins. First, they decrease the toxicity of the volatile, toxic drug. Second, they protect the drug within the vehicular reservoir from moisture to slow hydrolytic degradation.

Contraindications

There are important Contraindications to the use of dichlorvos. The drug should not be used within a few days of use or exposure to cholinesterase inhibitors.

An important source of exposure is routine use of these agents around the owner's premises.

Dichlorvos should not be used concurrently with other anthelmintics, tranquilizers, muscle relaxants, or modified live-virus vaccines. The drugs, which may also have actions on the CNS, skeletal muscle, and/or muscarinic receptors may increase the toxicity of dichlorvos. Presumably, the live-virus vaccines act as stressors that may exacerbate the toxicity.

Dichlorvos should not be used in animals with diarrhea or severe constipation or intestinal blockage.

Puppies and kittens weighing less than 1 lb and less than 10 days old are not good risks.

Dogs with heartworms should not be treated.

Advantages

Advantages of dichlorvos are that it is inexpensive and is effective against bots. Other organophosphates share these properties.

Disadvantages

The primary disadvantage is the low therapeutic index.

Levamisole (Imidazothiazole derivative)

Levamisole is the levo-rotatory form of tetramisol. The dextro isomer contributes to the toxicity, but not the therapeutic effect so it has been removed in marketed preparations. Levamisol restores cell-mediated immune function in peripheral T-lymphocytes and stimulates phagocytosis in monocytes.

Mechanism of Action

Levamisole causes nicotinic stimulation of ganglia and CNS in susceptible worms. Parasites are presumably much more sensitive to these effects than the host. Parasites are paralyzed and expelled alive. At higher concentrations, levamisole interferes with nematodal carbohydrate metabolism where it blocks fumarate reductase and succinate oxidase.

Spectrum

Adverse effects

Advantages

Advantages of levamisole are that it has a pour-on and an injectable dose form and affects larval stages dwelling in the tissues. It is also well-known for its ability to enhance immune function in animals with certain deficits. It does not appear to enhance a fully functional immune system.

Disadvantages

Disadvantages of levamisole include the adverse effects noted above.

Butamisole (Imidazothiazole derivative)

Butamisole is related to levamisole. It is supplied in a propylene glycol, benzyl alcohol base for injection subcutaneously. Preparations containing butamisole include Styquin.

Spectrum

The spectum of activity include whipworms and hookworms.

Adverse effects

The drug is free of serious adverse effects up to 3-times the recommended dose. Because dosing is important, it is recommended that 1.0 ml syringes be used when treating animals weighing less than 10 pounds.

Adverse effects include pain during injection, sterile abscess or seroma formation after injection, and transient listlessness.

Contraindications

In contrast to its relative levamisole, there are important contraindications to the use of butamisole indicating its greater toxicity. Butamisole is contraindicated in

Bunamidine apparently enhances the toxicity of butamisole since there have been reports of deaths when the drugs were used simultaneously.

Advantages

Advantages of butamisole are its effectiveness and, although not without toxicity, it is safer than some of the alternatives.

No fasting is required for use of butamisole.

It appears to have no negative effects on reproduction. It is safe during pregnancy and has no effect on male fertitility.

Butamisole can also be used safely with phenothiazine tranquilizers (e.g., chlorpromazine) and organophosphate products.

Disadvantages

Butamisole cannot be used in debilitated animals or animals with renal or hepatic disease. Its spectrum of activity is limited, involving primarily adult hookworms.

Piperazines

Lynn95* p247 on Selectivity -- Ascarids are very sensitive to piperazines, hookworms are refractory

Diethylcarbamazine citrate [CaracideR, HetrazanR, etc.]

Therapeutic use

Prevent development of infective larvae

No effect against adults

Actions against microfilariae, but are hazardous -- do not use in animals with microfilariae

PROPHYLACTIC -- MANY SCHEDULES

AVMA recommends -- 1.25 mg/lb (of base drug) per day during and 2 months following exposure to mosquitos.

If must alter dosage due to tablet size, adjust so that dose is on the high side.

Chemistry / Structure

Related to PIPERAZINE

Adverse effects

RELATIVELY NON-TOXIC.

GASTROINTESTINAL IRRITATION and VOMITION in few animals

Multiple generation studies -- no evidence of problems.

SEVERE REACTIONS in dogs that have circulating microfilariae

Organic Trivalent Arsenicals

Thiacetarsamide sodium , arsenamide [Caparsolate sodiumR, FilaramideR]

Chemistry / Structure

Therapeutic use

Historically, arsenicals were used for Rx of human syphilis and metazoan diseases

KILLS 98-100% of ADULT WORMS in 21 days.

dose of 0.1 ml/lb BID 2-3 days iv is from IVMA (of CAPARSOLATE SODIUM)

Pharmacokinetics

Elimination

Toxicity Levels --

Typical Dose and Schedule

Adverse effects

Precautions

Use of adjuvant therapy to reduce toxicity.

Treatment of Toxicity

Systemic toxicity

Melarsomine dihydrochloride, (ImmiticideR, RM340)

Adverse effects

Refs:

Over-The-Counter Anthelmintics

Many "wormers" are available at your corner drug or pet store without prespcription. Veterinarians should be generally familiar with these less effective products because many of the clients will know them well. Generally, these are old drugs that have significant disadvantages when compared to newer drugs released recently.

n-Butyl Chloride

This drug, which is present in many comercial preparations is given orally to dogs and cats after 18-24 hr fast for Ascarids and some effect on hookworms. One should follow

with a cathartic 1 hr after treatment. The animal can be fed within 4-8 hours after treatment. Occasionaly, the animal may vomit, but otherwise it is relatively safe. The drug is HIGHLY FLAMMABLE.

Toluene (!yes!)

Toluene is present in may commercial preparations. It is flammable, i.e., it burns. It comes in gelatin capsules.

Adverse effects

Toluene is safe for mammals on an acute basis, but long term, repeated exposure to any aromatic hydrocarbon is inadvisable. "Overdosage produces transitory incoordination, muscle tremors, vomiting, and central nervous system depression." Theodorides 1985.

Treatment of toxicity caused by toluene includes warm water gavage (flush stomach via the mouth with a tube), mineral oil, and oxygen therapy. One should avoid the use of digestible oils, alcohol, and epinephrine as emergency treatment. Toluene will partition into oil based solvents. Because mineral oil is neither digested nor absorbed, this is tantamount to elimination. Digestible oils, however, will release the tolene as they are digested, allowing it to be absorbed as well.

Use/comments

Toluene is inconvenient to use because one should fast animals 12 hours before and 4 hours after treatment.

Toluene is used to remove ascarids and hookworms of dogs and cats. It has some activity against whipworms e.g., Trichuris vulpis.

REFERENCES

New Refs not used in preparing these notes, yet.

Random Notes that need to be included in appropriate place in antiparasitic notes.


| Drug Groups | | top |
Gordon L. Coppoc, DVM, PhD
Professor of Veterinary Pharmacology
Head, Department of Basic Medical Sciences
School of Veterinary Medicine
Purdue University
West Lafayette, IN 47907-1246
Tel: 317-494-8633Fax: 317-494-0781
Email: coppoc@vet.purdue.edu

Last modified
8/16/96 GLC